It was a rash that made Dr. Alisa Femia realize.
Femia, director of hospital dermatology at NYU Langone Health in New York City, was looking at a patient file, which included several photos of the 45-year-old man who had been caring for his wife while she was ill for the past few weeks. of Covid19. The man had dark red circular spots on the palms of his hands and soles of his feet. Her eyes were pink and her lips were extremely chapped.
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His body was exploding with the kind of extreme inflammation seen almost exclusively in children at the time.
“Before I even saw the patient,”
MIS-A stands for “Multisystem Inflammatory Syndrome in Adults”. When the condition was identified in babies this spring, it was called MIS-C, with the C standing for “babies.”
The children were developing dangerous inflammation around the heart and other organs, often weeks after their initial infections with SARS-CoV-2, the virus that causes Covid-19.
The Centers for Disease Control and Prevention alerted MIS-C doctors in May. As of October 1, the CDC had reported 1,027 confirmed cases of MIS-C, with more cases under investigation. Twenty children died.
In some cases, children have developed rashes like the one Femia noticed in her adult patient.
Femia and colleagues posted the details of the case in The Lancet in July to alert other doctors to be on the lookout for similar patients.
“The skin is right there in front of your eyes,” Femia said. “You can’t miss it.”
But many doctors may not recognize the condition in adults. Only a few dozen cases of MIS-A have been reported. And not all patients have obvious rashes.
Dr. Sapna Bamrah Morris, clinical director of the Health Systems and Worker Safety Task Force, part of the CDC’s Covid-19 response, detailed 27 cases in a report released by the agency last week.
The “true prevalence of MIS-A is unknown,” Morris said. “We have to get doctors to realize this. It may be rare, but we don’t know. It may be more common than we think.”
Part of the problem is that the virus has been circulating among humans for less than a year. Doctors around the world are still learning how SARS-CoV-2 works in patients.
Typically, seriously ill Covid-19 patients tend to arrive at the hospital because they have difficulty breathing. This was not the case with MIS-A.
Many MIS-A patients report fever, chest pain or other heart problems, diarrhea, or other gastrointestinal problems, but not shortness of breath. And diagnostic tests for Covid-19 tend to be negative.
Instead, patients will test positive for Covid-19 antibodies, which means they were infected two to six weeks earlier, even if they never had symptoms.
It may be rare, but we don’t know. It may be more common than we think.
“Just because someone doesn’t present with respiratory symptoms as their primary manifestation doesn’t mean what they’re experiencing isn’t the result of Covid-19,” Morris said.
The disease can be life-threatening. Patients usually have some type of severe dysfunction of at least one organ, such as the heart or liver.
Ten patients in the CDC report were to be admitted to the intensive care unit. Some had to be put on fans. Two died.
Furthermore, the CDC report showed that members of racial and ethnic minority groups appear to be disproportionately affected. Almost all MIS-A patients were African American or Hispanic. But too few cases have been reported to fully understand the underlying mechanisms at play.
While some kind of genetic link may be possible, Covid-19 has been shown to “disproportionately affect underrepresented minorities, possibly due to socioeconomic factors,” Femia said. Underlying health conditions that increase the risk of complications of Covid-19, such as obesity and type 2 diabetes, also tend to be more prevalent among members of racial and ethnic minorities.
Over the summer, doctors in Florida started seeing spikes in Covid-19 cases. Dr. Lilian Abbo, chief of infection prevention for the Jackson Health System in Miami, recalls that “a very high volume of people who pass through our emergency wards or hospitals become seriously ill.”
The more sensitive and reliable test for Covid-19, called the PCR test, was not always available and it could take several days to return the results. Abbo turned to antibody testing to have the influx of patients transferred to a Covid-19 unit or elsewhere in the healthcare system.
People generally develop antibodies to an infection within about a week. It would at least give Abbo and his colleagues an indication that Covid-19 was involved in some way in their patients’ symptoms, he reasoned.
It was then that Abbo discovered a subset of patients who were seriously ill after having Covid-19, but without the lung problems that are telltale of an acute infection.
“We were a little baffled,” Abbo said. “We did the molecular PCR tests and they would be negative. Then the antibody tests were positive.”
Further blood tests revealed extremely high levels of inflammation in the body.
Additionally, while most seriously ill Covid-19 patients tend to be over 65 or have multiple underlying health problems, these patients “were younger people who would not be expected to get sick,” Abbo said. .
“This is what caught our attention.”
There is no proven treatment for MIS-A. “We need to recognize this syndrome and develop data” to understand which therapies may be most effective, Abbo said. “We’re just shooting blind.”
Dr. Jill Weatherhead, assistant professor of infectious diseases and tropical medicine at Baylor College of Medicine in Houston, points out that the CDC case reports show that doctors have tried a variety of medications for MIS-A patients, including steroids and drugs that could affect the immune system, called interleukin-6 inhibitors.
“The problem with these diseases is that we don’t know the mechanisms that are causing MIS-A and MIS-C,” Weatherhead said. “It is difficult to know what the standard treatment should be until we have more information.”
In children, MIS-C is usually treated with intravenous immunoglobulin, a blood product containing a variety of antibodies. It can also be used for adults, but the effects are largely unproven.
Intravenous immunoglobulin, or IVIG, is different from another blood-derived antibody treatment, convalescent plasma. The latter is taken from patients who have recovered from Covid-19 and have antibodies specifically targeted to the virus in their blood. IVIG, on the other hand, is more of a medley of antibodies that are not specific to the coronavirus.
The idea is that MIS-A patients already have Covid-19 antibodies, so adding more with the convalescent plasma is unlikely to help.
The current theory for MIS-A patients is that “the infection, as far as we know, is gone,” said Dr. Hugh Cashier, director of critical care services for Sandra Atlas Bass Heart Hospital at North Shore University Hospital. , part of Northwell Salute, on Long Island, New York.
“It’s the antibodies that have been produced that appear to be causing a problem,” he said.
Cashier was part of a large team of doctors who treated the wave of Covid-19 patients in New York this spring. Although MIS-A was not identified at the time, Cashier is convinced that such patients have always existed.
“We were seeing patients who got admitted to ICU with organ failure,” Cashier said. They would have tested negative for Covid-19, he said, but would have tested positive for Covid-19 antibodies, suggesting they had been infected previously.
“If you look back, they probably had this multi-systemic inflammatory syndrome,” Cashier said. “We didn’t have all the pieces to put together.”
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Months later, the puzzle begins to unfold. But a comprehensive approach will be needed to identify MIS-A patients.
“This must be at the forefront of the mind of every ICU doctor who sees patients, especially when they have Covid-19 antibodies,” Cashier said.
Given Femia’s experience, this includes those who specialize in dermatology.
“This is truly the beauty of medicine, where, for this syndrome, many different specialists have to come together to help make the diagnosis,” Femia said.
Doctors fear that many MIS-A patients will go undetected and possibly not treated.
“There isn’t enough data to tell you what the long-term effects of this might be,” Cashier said. “This could be the tip of the iceberg. This is what worries me.”
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